Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation

Abstract

Vitamin D has emerged as a central player in the immune system, with its deficiency being implicated in the pathogenesis of several autoimmune diseases, including chronic GvHD. This is a retrospective cohort analysis of 166 patients, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at the Karolinska University Hospital, evaluating GvHD, graft failure, infectious complications and survival after HSCT in relation to pre-transplantation vitamin D levels. Most of the patients were deficient in vitamin D before HSCT (median 42 nmol/L). In multivariate analysis, vitamin D level before HSCT was identified as a significant independent risk factor for development of cGvHD. The increased incidence of cGvHD was not coupled to better disease-free survival; instead there was a trend towards lower overall survival in the vitamin D-deficient patients. In addition, we found a significant correlation between vitamin D deficiency and incidence of CMV disease, with no case of CMV disease occurring in patients with sufficient levels of vitamin D before HSCT. Our results support a role of vitamin D in immune tolerance following HSCT. These findings could be highly relevant for the care of HSCT patients, and prospective, randomized studies on the effect of vitamin D supplementation are therefore needed.

Is autoimmunity the Achilles' heel of cancer immunotherapy?

“…Many epidemiologic studies indicate that vitamin D deficiency is associated with an increased risk of cancer incidence and mortality 78 . There is an increased incidence of GVHD in patients who have vitamin D deficiency before undergoing allogeneic HSCT 79 . Both macrophages and T reg cells are implicated in the above studies.…”

Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production

“…Further, in vitro assays of both CD41 + zebrafish HSCs and CD34 + hUCB HSPCs revealed cell autonomous responses to short-term, low-dose 1,25(OH)D3 supplementation, independent of the niche, increasing multi-lineage CFU numbers via VDR-mediated alterations in proliferation and survival. These data are particularly relevant in the context of clinical observations of vitamin D-deficient pediatric and adult HSC transplant recipients who demonstrate a poor outcome, including graft versus host disease, delayed time to neutrophil engraftment, and overall survival (von Bahr et al, 2015; Wallace et al, 2015). Together, our data indicate that, beyond the published effects on lineage differentiation and immune-regulation, vitamin D has an important role in the foundation of the hematopoietic tree, regulating definitive HSPC numbers in the embryo.…”

A Case With Vitamin D Deficiency-Induced Cytomegalovirus Enteritis Presenting as Bowel Pseudo-Obstruction

“…Vitamin D deficiency was reported associated with disorders of the immune system, such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis and rejection of solid organ allografts [3]. Vitamin D also has a protective effect against infections.…”

“…The two antimicrobial peptides under the influence of vitamin D are LL-37 (cathelicidin) and β-defensin 2, which have activity against several bacteria, as well as viruses and fungi [10]. One retrospective cohort analysis of 166 patients who underwent allogeneic hematopoietic stem cell transplantation found that low vitamin D levels represent a significant risk factor for CMV disease [3]. …”

“…While involving the gastrointestinal tract, the site most commonly affected is the colon, followed by the duodenum, stomach, esophagus and small intestine [2]. Vitamin D, measured as 25-OH-D3, has emerged as a central player in the immune system, and deficiency of vitamin D carries a risk factor of infections [3]. We report a case of CMV jejunitis in a 67-year-old woman who had low vitamin D level and presented with a sign of bowel pseudo-obstruction.…”